This study provides first clinical evidence for the implication of a "glioma stem cell" or "self-renewal" phenotype in treatment resistance of glioblastoma. Biologic mechanisms identified here to be relevant for resistance will guide future targeted therapies and respective marker development for individualized treatment and patient selection.

Highlights d Leukocyte invasion is higher in brain metastasis than in CNSendogenous cancers d The tumor type shapes the differentiation of monocytederived macrophages d Brain metastases harbor a high frequency of regulatory T cells d Both activation and exhaustion are prevalent in lymphocytes of the metastatic TME